BIOLOGICAL MUTAGENES AND THEIR ROLE IN THE NATURAL MUTATION PROCESS

Two sets of lethal mutations in chromosome 2 of Drosophila melanogaster have been tested for alletism: lethals induced by viruses and exogenous DNA and those found in different natural populations or arising de novo in the progeny of wild-type flies. It was concluded that the mutagenic effect of different viruses and other sources of DNA, exogenous for the host cells, is to induce single-locus and multiple mutations, which can spread throughout natural populations. Certain population-genetical consequences of the data obtained are discussed, and in particular, the position that during virus-in­ duced mutagenesis, similar multiple chromosome lesions can occur repeatedly and in­ dependently in isolated populations of flies a result of a single mutation event.

A long-term analysis of the appearance of mutations and their distribu tion in geographically isolated populations of Drosophila indicated that biocenotic interactions of viruses (and their genomic components) with the host genome could serve not only as a powerful selective factor, but could also lead to an intensification of the rate of the mutation process and to the activation of mobile elements of the genome [1,2].A manysided investigation of the mutagenic effect of exogenous DNA and dif ferent viruses, noninfectious for Drosophila, led to the same conclu sion [3][4][5].
From the viewpoint of population and evolutionary genetics, it is not only the principle of virus and exogenous DNA mutagenicity, firmly established by many works which is interesting, but also the direct de termination of which kind of hereditary changes, associated with the ef fect of these factors, are distributed in natural populations.The possibi lity of answering this question appeared after comparing two sets of se cond chromosome lethals obtained and analyzed during many years in two fabofatories: (a) induced by DNA and RNA viruses and foreign DNA [4,5] and (b) isolated from natural populations in the USSR fl].The suitability of an investigation of lethals in the case of Drosophila for these purposes is obvious, since lethals represent an objectively registerable class of mutations, which occur in not less than 80 % of loci in the genome.Moreover, reasonable simple methods are available, which make it possible to isolate and localize lethals in a particular chromo some, and to study their allelic relationships.So both sets of lethals we re studied for allelism and some of them were localized.
The mutagenic effect both of various viruses noninfectious for Dro sophila and foreign DNA is characterized bv strong site-specificity.Ana lysis of even small samples consisting of 15-20 lethal chromosomes shows comnlex allelic reactions and high allelism freauency.The mutati ons occur in definite grouos of loci specific for each agent tested [5].The chromosomes with lethal defects in many sites (multilethal) appear regularly (see Fig. 1).The mutant loci are either clustered or dispersed among the chromosome.
On the contrary, allelic relations of large grouns of lethals isolated from nature are rather simple.The mutations usually aopear in a great number of loci.Some lethals, however, have been found reneatedly both within one population and among adjacent ones.The multilethal chro-mosomes were also isolated (see Fig. 2).Among these groups of natu ral lethals wee found allelism with the lethals induced by viruses and foreign DNA (see Table ).
The main conclusion are: (1) mutagenic action of different viral agents and foreign DNA sources causes the multisite mutations which may be distributed in natural populations; and (2) this form of muta genesis is similar to the action of movable genetic elements [7][8][9].In both cases the site-specific chromosomal lesions (inclu ding rearrangements) may occur due to single mutation events.Similar multisite mu tations may appear repeated ly and independently in iso lated populations.
Thus viruses and vario us types of DNA-carriers when entering the eukaryotic genome, can sharply in tensity the rate of mutagene sis, can lead to site-specific multiple chromosome lesions, Fig. 1  and can induce instability of the genes.It becomes increasingly obvious that the interaction of various DNA-and RNA-carriers plays a substan tial role in the natural mutation process [10].Having presented this vi ewpoint, we are able to explain a series of baffling phenomena in popula tion genetics and cytogenetics: the mode of mutation in particular genes, Fig. 2. Diallelic crosses between 34 chromosomes with lethals isolated from a natural population in Dilizhan (Armenia) in 1964.Allelic relationships as a rule are simple.One exclusion is shown at left.Chromosome 233 contains two closely linked lethals; both of them were allelic to the virus induced mutations (see Table ).Chromosome 255 carries a short inversion on the right arm, In (2R); 51 A; 57B which arises synchronously in remote regions; outburst of mutability ac companied by the appearance of multiple unstable alleles; the presence of similar multiple crossovers in different parts of an area occupied by the species, etc.We arrive at biocenotic and at the hypothesis that the main factor in the natural mutational process is the interaction of components of the biocenosis.

*
In the test for aUeUsm we compared 64 chromosomes with lethals, frequently met in natural populations, with the indicated samples of induced lethals in 72-64-4608 crosses; ** In brackets we indicate the nucleic acid of the particular virus; ***.The lethal mutations were isolates in the progeny of flies infected with picornavirus subtype C, pathogenic for Drosophila[6].